Enantiomeric separation and sensitive detection of propranolol, metoprolol and atenolol derivatized with a fluorogenic reagent, 4-(N-chloroformylmethyl-N-methyl)amino-7-N,N-dimethylaminosulf onyl-2,1, 3-benzoxadiazole (DBD-COCl), on cellulose chiral columns in the reversed-phase mode.
An electrophilic fluorogenic reagent, 4-(N-chloroformylmethyl-N-methyl)amino-7-N,N-dimethylaminosulfo nyl-2,1,1,3-benzoxadiazole (DBD-COCl), was used to react with three beta-blockers, propranolol, metoprolol and atenolol, to yield the derivatives which were subsequently verified to be amide compounds (1:1 adducts) derived from the reaction with the secondary amino group of the beta-blockers. DBD-COCl exhibited high reactivity for the reaction completed within 5 min under mild conditions and without any need for a catalyst. The derivatives were well separated enantiomerically on cellulose CSPs (the derivative of propranolol on a Chiralcel OD-R column and those of metoprolol and atenolol on a Chiralcel OJ-R column) in the reversed-phase mode, with the S-configurations being eluted before the R-configurations. The derivatives were stable at 4 degrees C for 1 week. The detection limits (S/N = 3) were 50 fmol for both (S)- and (R)-propranolol, 12 and 17 fmol for (S)- and (R)-metoprolol, respectively, and 15 and 20 fmol for (S)- and (R)-atenolol, respectively.
Yang
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X
Graduate School of Pharmaceutical Sciences, University of Tokyo, Japan.
Fukushima
T
T
Santa
T
T
Homma
H
H
Imai
K
K
D000319:Adrenergic beta-Antagonists / Q000032:analysis*; D001262:Atenolol / Q000032:analysis; D002850:Chromatography, Gel / Q000379:methods; D002851:Chromatography, High Pressure Liquid; D007202:Indicators and Reagents; D008790:Metoprolol / Q000032:analysis; D010069:Oxadiazoles; D011412:Propanolamines / Q000032:analysis*; D011433:Propranolol / Q000032:analysis; D013237:Stereoisomerism
D000319:Adrenergic beta-Antagonists; D007202:Indicators and Reagents; D010069:Oxadiazoles; D011412:Propanolamines; C089192:4-(N-chloroformylmethyl-N-methyl)amino-7-N,N-dimethylaminosulfonyl-2,1,3-benzoxadiazole; D001262:Atenolol; D011433:Propranolol; D008790:Metoprolol